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The proteasome is a highly regulated complex fundamental for cell homeostasis and a target for cancer therapy. Here the authors use cryo-EM and single-particle analysis to obtain a detailed map of the interactions between each active sites of the core 20S proteasome and the irreversible inhibitor AdaAhx₃L₃VS.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

The APC/C is a large multiprotein complex that functions as an E3 ubiquitin ligase to regulate the cell cycle. Here, the entire APC/C complex is reconstituted, and in combination with structural studies a pseudo-atomic model for 70% of the complex is provided. These results contribute towards a molecular understanding of the roles of individual subunits in APC/C assembly and their interactions with co-activators, substrates and regulatory proteins.

Drug resistance remains a major challenge in cancer treatment. Here, the authors identify Connexin43 as target that enhances BRAF/MEKi efficacy by interfering with DNA repair pathways, overcoming drug resistance. They develop an mRNA therapy that improves efficacy and sensitizes resistant cells.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

The anaphase promoting complex/cyclosome (APC/C) is a large multimeric ubiquitin E3 ligase that regulates the eukaryotic cell cycle in processes such as chromatid segregation and completion of mitosis. It catalyses the polyubiquitylation of a diverse array of mitotic regulatory proteins and targets them for proteasomal degradation. Target selection also involves a co-activator protein (either Cdc20 or Cdh1) together with core APC/C subunits. Here, a cryo-EM structure of APC/C^Chd1 bound to a D-box peptide substrate is presented. The structure provides important insight into the recognition and catalytic mechanism of APC/C substrates.

Here, the authors present results of the ZiBRA-2 project (https://www.zibra2project.org) which is an arbovirus surveillance project, across the Midwest of Brazil using a mobile genomics laboratory, combined with a genomic surveillance training program that targeted post-graduate students, laboratory technicians, and health practitioners in universities and laboratories.

A study introduces curcumin biosynthesis in Arabidopsis by expressing the turmeric genes DIKETIDE-CoA SYNTHASE and CURCUMIN SYNTHASE 2, and the monomers curcumin and phenylpentanoids were successfully incorporated into the lignin cell wall to enhance biomass processing.

The authors report genome-wide data from 34 ancient individuals spanning the Holocene, from what is now Brazil, illuminating connections and disjoints between Sambaqui shellmound societies and preceding and later peoples.

Analysis of individual-level patient records from Brazil reveals that the extensive shocks in COVID-19 mortality rates are associated with pre-pandemic geographic inequities as well as shortages in healthcare capacity during the pandemic.

An analysis of viral genomes and epidemiological data from the 2022 mpox outbreak in Portugal sheds light on the heterogeneity of early transmission events, with national and international linkages.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

Protection against SARS-CoV-2 infection involves T cell and B cell responses but only studying one or the other has proved difficult. Here the authors immunise with a fusion protein construct of N and RBD proteins from SARS-CoV-2 and find that this promotes protection in animal models preferentially via T cells.

Merbl and colleagues demonstrate that high expression of the proteasome regulator PSME4 is associated with immune-cold lung tumors and reduced antitumor immune responses, by functioning to modulate the protein degradome and antigen diversity.

Gram-negative bacteria use type III secretion systems (T3SSs) to pass virulence factors into host cells, making them potential therapeutic targets to combat bacterial infection. A new EM study of the needle complex from the Shigella T3SS reveals 12-fold symmetry throughout and suggests interactions important for self-assembly and complex stability.

The biogenesis of eukaryotic 20S proteasomes requires the accurate assembly of 14 closely related protein subunits and occurs in a complex series of chaperone-dependent steps. Important insights into this pathway are now provided by the high-resolution cryo-EM structures of two 20S proteasome assembly intermediates.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

Accounting for inter- and intraspecies evolutionary relationships is important for conservation planning, but rarely considered in practice. A new framework identifies priority conservation areas accounting for evolutionary diversity.

Borges et al. study the dynamics of SARS-CoV-2 in Portugal during 2020. The authors use phylodynamic modelling to infer patterns of SARS-CoV-2 introduction into Portugal and its subsequent spread, providing a comprehensive genomic epidemiology study of the early SARS-CoV-2 epidemic in Portugal.

Structural and functional characterizations show that the specificity of the Plasmodium falciparum proteasome is sufficiently unique from that of the human proteasome to allow selective targeting with inhibitors.

A ubiquitin binding domain in the IAP proteins binds Lys 63-linked poly-ubiquitin chains and is essential for the oncogenic potential of cIAP. This domain is also required for activating NF-κB, possibly by binding poly-ubiquitinated NEMO.

Jorge Reis-Filho and colleagues identify recurrent mutations in PRKD1 in 73% of polymorphous low-grade adenocarcinoma, a malignant tumor of the minor salivary glands. The mutations cause activation of the PRKD1 serine-threonine kinase.